{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T05:09:34Z","timestamp":1778389774209,"version":"3.51.4"},"reference-count":179,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"This work was supported and funded by the Deanship of Scientific Research at Imam Mohammad Ibn Saud Islamic University","award":["(grant number IMSIU-DDRSP2602)"],"award-info":[{"award-number":["(grant number IMSIU-DDRSP2602)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cancer therapy is increasingly shaped by the need for agents that are both mechanistically precise and clinically tolerable. Sulforaphane (SFN), a dietary isothiocyanate enriched in cabbage-family vegetables such as cauliflower and Brussels sprouts, has emerged as a pleiotropic modulator of tumor biology. This review synthesizes current evidence that SFN regulates diverse cancer-relevant processes, including redox homeostasis, cell-cycle progression, apoptosis, autophagy and epigenetic remodeling, largely through coordinated effects on transcriptional (for example, Nrf2, MAPK, NF-\u03baB and AP-1), post-transcriptional (microRNAs and messenger RNAs) and epigenetic (DNA methyltransferases and histone deacetylases) networks. We then examine how functional nucleic acids, including aptamers, small interfering RNAs, microRNAs and tetrahedral DNA nanostructures, can be engineered to guide SFN to tumor cells, amplify pathway-specific effects and overcome resistance. Particular emphasis is placed on nanotechnology-enabled delivery platforms that enhance SFN stability, bioavailability and tumor selectivity. Finally, we outline key challenges, such as context-dependent Nrf2 activity, inter-individual variability in metabolism and incomplete clinical validation, and propose priorities for translating SFN-based functional nucleic acid systems into rational, combination-ready strategies for precision oncology.<\/jats:p>","DOI":"10.3390\/ijms27094033","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T13:32:21Z","timestamp":1777555941000},"page":"4033","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sulforaphane-Activated Functional Nucleic Acids for Cancer Therapy: Mechanisms, Delivery Strategies, and Nanomedicine Advances"],"prefix":"10.3390","volume":"27","author":[{"given":"Mukesh","family":"Kumar","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6382-8807","authenticated-orcid":false,"given":"Nasir A.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shafiq Ur","family":"Rahman","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevaun Altamon George","family":"Wilson","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salwa","family":"Eman","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8814-5957","authenticated-orcid":false,"given":"Nosiba S.","family":"Basher","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3493-6451","authenticated-orcid":false,"given":"Walid","family":"Elfalleh","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed Osman Abdalrahem","family":"Essa","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"College of Veterinary Medicine, Albutana University, Rufaa 22217, Sudan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1314-8066","authenticated-orcid":false,"given":"Ahmed A.","family":"Saleh","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"},{"name":"Animal and Fish Production Department, Faculty of Agriculture (Al-Shatby), Alexandria University, Alexandria City 11865, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8993-3507","authenticated-orcid":false,"given":"Hosameldeen","family":"Mohamed Husien","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"},{"name":"College of Veterinary Medicine, Albutana University, Rufaa 22217, Sudan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengzhi","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"},{"name":"Joint International Research Laboratory of Agriculture & Agri-Product Safety of MOE, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. 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